Certain tetrahydro-7-oxobenzo[b]thien-4-ylurea compounds and certain tetrahydro-4-oxo-1-naphthylurea compounds are useful as growth-promoting agents for animals such as poultry, fur-bearing and farm animals. These compounds may be graphically illustrated and defined in general terms by formulae (A) and (B) as follows: ##STR1## wherein the R groups R' to R"" each represent hydrogen or some other moiety, selected to enhance the biological activity of said formulae (A) and (B) compounds.
The above oxo- compounds may be prepared from the corresponding urea compounds by oxidation of the ring-activated .alpha.-methylene group to a keto (oxo) group as schematically illustrated below: ##STR2##
Alternatively, formulae (A) and (B) compounds, wherein the R groups R' to R"" each are hydrogen, may be prepared from the corresponding oxo-amines of formulae (C) and (D) by reacting same with sodium or potassium cyanate, as schematically illustrated below: ##STR3##
Substituted ureas of formulae (A) and (B) may be prepared by treating the amines of formulae (C) and (D) with an appropriately substituted isocyanate of formula: R'-NCO or with a carbamoyl halide of formula: ##STR4## wherein R' and R" are as hereinabove-identified, and the halogen is bromine or chlorine.
The ring-activated .alpha.-methylene groups of the precursors of compounds of formulae (A) to (D) may be oxidized, using 2 to 8 mole equivalents, and preferably 4 to 8 mole equivalents, of an oxidizing agent selected from the group consisting of ceric ammonium nitrate, silver oxide or sodium bichromate at a temperature between about 0.degree. C. and 100.degree. C., and preferably 20.degree. C. to 60.degree. C., in a solvent selected from the group consisting of aqueous solutions of acetic acid, acetonitrile, tetrahydrofuran, dioxane, dimethoxyethane, diethylene glycol dimethyl ether, which may contain nitric acid, phosphoric acid or perchloric acid; or the oxidizing agent chromic anhydride in acetic anhydride followed by hydrolysis.
These oxidation reactions, while yielding the desired animal growth regulating compounds of formulae (A) and (B) or their respective precursors (C) and (D), leave much to be desired. In general, the above oxidation reactions afford the products usually in very low yields; large molar excesses of oxidizing agents (some of which are quite expensive) are needed; the reactions usually do not lend themselves readily for scale-up, and some of them represent fire and/or explosion hazards.
Clearly, there is a need for an oxidation process which would yield the above-described compounds of formulae (A) to (D) in satisfactory yields, and which would be free of the undesirable features of the above-referred-to oxidation processes.
It is, therefore, an object of the present invention to provide an improved oxidation process, employing potassium permanganate, for the preparation of the hereinabove generically identified tetrahydro-7-oxobenzo[b]thien-4-ylurea and tetrahydro-4-oxo-1-naphthylurea compounds of formulae (A) and (B), and their respective precursors, the compounds of formulae (C) and (D).